Presented as an abstract at the European Hematology Association 2021 Virtual Congress, the study results showed the novel combination resulted in early disease modification among 34 patients.
Adding navitoclax to ruxolitinib for the treatment of myelofibrosis (MF) may yield benefits for patients not responding to ruxolitnib alone, suggests data from a phase 2 multicenter study.
Presented as an abstract at the European Hematology Association 2021 Virtual Congress, the study results showed the novel combination resulted in early disease modification among 34 patients, offering a potential treatment for patients on ruxolitinib monotherapy who need a different treatment option.
“JAK inhibitors are the standard of care for intermediate- and high-risk patients, though they exhibit little impact on bone marrow fibrosis (BMF),” explained the researchers. “However patients who do not respond, or develop secondary resistance to ruxolitinib, have limited therapy options.”
Nine of the patients achieved a spleen volume reduction of ≥35% (SVR35) at Week 24—the study’s primary endpoint—and another 6 patients achieved the reduction at any point during the study.
The data also showed that nearly 1 in 3 patients (30%; 6 of 20 patients) achieved a ≥50% reduction in total symptom score at week 24—a secondary endpoint of the study—and another 41% (12 of 29 patients) achieved the reduction at any point during the study.
“These data are the first to show both SVR improvement associated with decrease of cytokines and TSS improvement in the same patient cohort,” wrote the researchers, adding, “These data suggest that navitoclax combined with ruxolitinib may exert disease-modifying activity in MF and support further investigation in phase 3 clinical trials (NCT04472598 and NCT04468984).”
Notably, at a median follow-up of 21.6 months, the median overall survival was not reached among the patients, more than half (52%) of which harbored at least 3 mutated genes and 58% of which had high molecular risk.
Patients included in the study received ruxolitinib for at least 12 weeks and had been on a stable dose of ≥10 mg twice daily for at least 8 weeks before receiving their first dose of navitoclax. Throughout the study, patients continued their ruxolitinib treatment and received oral navitoclax at a starting dose of 50 mg/day before the dose escalated weekly to a maximum of 300 mg/day.
Data from the phase 2 trial also showed that the novel combination was well tolerated. The most common adverse events (AEs) were thrombocytopenia (88%), diarrhea (71%), and fatigue (62%). According to the researchers, thrombocytopenia without clinically significant bleeding (56%) and anemia (32%) were reversible upon dose modification of the combination.
There were 15 patients (44%) who experienced a serious AE, the most common being pneumonia (12%), and navitoclax discontinuation, reduction, or interruption was reported in 5 patients, 26 patients, and 22 patients, respectively.
Harrison C, Garcia J, Somervaille T, et al. Navitoclax and ruxolitinib for patients with myelofibrosis and JAK inhibitor experience: response duration in a phase 2 study. Presented at: EHA 2021. Abstract EP1078.